Apropos of hypertension, it is important to control blood pressure steadily below certain pressure because preventing coronary artery diseases such as stroke, cardiac failure and myocardial infarction, and cardiovascular complication such as renal insufficiency which threat life by keeping blood pressure in the normal range is more important than treating blood pressure directly. Selection of a therapeutic agent should be made carefully because therapeutic agent for blood pressure is required to be administered in long-term. Therefore, side effects incurred from long-term use of drug are needed to be reduced by combining drugs having different mechanisms rather than selecting only one drug and by reducing drug dosage via the combined administration for keeping blood pressure in the normal range over long periods.
However, there are problems such as decrease of medicinal effect and incurrence of side effects due to drug combination because absorption, metabolism, distribution, expression of drug effect, and excretion-related transporter, metabolic enzyme and gene of each drug have different property and show different actions when taking two or more ingredients. For instance, drug can cause problems in absorption, metabolism and excretion in everywhere at every phase such as the first phase of passing the intestinal wall, the second phase of influx into the liver, the third phase of activation via metabolized in the hepatocyte and the fourth phase of leakage from the hepatocyte through the biliary tract among others. Especially, disintegration and dissolution patterns of active ingredients according to pH cause a lot of problems in drug effectiveness when performing complex treatment.
Angiotensin II receptor blocker (ARB) is a drug effective in depressing blood pressure in both myocardial systole and diastole by blocking conjugation of angiotensin II which is one of the original substances that causes vasoconstriction with AT1 receptor among angiotensin receptors, and there are about 10 series of compound group including pharmaceutically acceptable salt. Also, these are being used for hypertension-related symptoms solely upon patients having mild through moderate symptoms or with angiotensin converting enzyme inhibitor which exhibits anti-hypertensive effect in similar mechanism [Angiotensin II Receptor Antagonist: An Overview, Am. J. Health-Syst. Pharm. 57(13): 1231-1238, 2000].
Fimasartan, one of the angiotensin II receptor blockers (ARB), is 2-n-butyl-5-dimethylaminothiocarbonylmethyl-6-methyl-3-[[2-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]pyrimidin-4(3H)-one and has a chemical formula 1, and it is approved under the title of KANARB® and currently available in the market (Korean Patent Registration No. 10-1058284).

HMG-CoA reductase inhibitor has effects of decreasing blood lipid concentration and cholesterol by preventing the reduction of HMG-CoA to be mevalonate, and thus it is used for hyperlipidemia, hypercholesterolemia and atherosclerosis.
Rosuvastatin, one of the HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitor, is (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid and has a structure of chemical formula 2, and it controls synthetic pathway of cholesterol and it is approved under the title of CRESTOR® and currently available in the market (Korean Patent Registration No. 10-0105432).

Fimasartan and rosuvastatin combination preparation having different acting mechanisms can be used for hypertension treatment but these combination preparation have a problem of affecting disintegration and dissolution of each active ingredient due to effect of interference to each other. That is, fimasartan exhibits decent solubility pattern under comparatively high pH media such as purified water and pH 6.8 dissolution media, but its solubility decreases under low pH media (i.e. pH 1.0-pH 4.0) and KANARB® which is a currently available fimasartan formulation in the market exhibits similar solubility pattern.
According to the properties of fimasartan explained above, problem of decreasing disintegration and dissolution due to interference between fimasartan and rosuvastatin is raised when preparing combination preparation with rosuvastatin. Especially, decrease of dissolution under low pH media could seriously affect bioavailability at the stomach where initial disintegration and dissolution occurs at the time of oral administration.
Under these circumstances, a research on a method of keeping constant disintegration and dissolution rates of fimasartan and rosuvastatin in spite of pH variation in the normal stomach is required.